Eight Weeks Sofosbovir/Ledipasvir in HCV Infected Children Aged 4 to 10 Years

Not Applicable

Completed

• Conditions: Hepatitis C, Chronic; Children, Only
• Interventions: Drug: Sofosbovir/Lepipasvir (200/45mg) tablet (Heterosofir)

• Registration Number: NCT03764345
• Lead Sponsor: National Liver Institute, Egypt

Brief Summary

Recently the era of direct-acting antiviral drugs for hepatitis C treatment has changed the world map of HCV. Results in adults are promising. FDA approved only two drugs in the pediatric age group 12 to 17 years. Younger children are still on the wait list for treatment. The current study aimed to treat children aged between 3 and 12 years with half the adult dose of Sofosbuvir/Ledipasvir combination (Heterosofir).

Detailed Description

The WHO has declared hepatitis C a global health problem, with ∼ 3% of the world's population (roughly 170-200 million individuals) infected with HCV. Egypt has the highest prevalence of HCV in the world, ranging from 6 to 28%, with an average of ∼ 13.8% in the general population. Ap-proximately 90% of Egyptian HCV isolates belong to a single subtype, 4a.

Hepatitis C virus (HCV) is a major cause of chronic liver disease and a prin-cipal reason for liver transplant; approximately 170 million people worldwide are chronically infected. There is general consensus that HCV elimination is associated with strong and sustained CD4+ and CD8+ T cell res-ponses that target multiple epitopes within the different HCV proteins, however, they are not maintained in patients who develop chronic disease . A variety of factors purportedly contribute to the dimi-nished T cell responses observed in chronically infected patients, including an im-paired dendritic cell (DC) function.

The successful development of direct-acting antivirals (DAAs) that are active against hepatitis C virus has transformed chronic hepatitis C infection from a con-dition requiring complex therapies with unsatisfactory outcomes to one that can be easily treated with few contraindications and side-effects. Since 2011, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved eight oral DAA regimens for the treatment of adults with chronic hepatitis C. Investigation into DAAs for children has been slower.

For adolescents aged 12-17 years, the safety and efficacy of the fixed-dose combination sofosbuvir and ledipasvir for genotype 1 or 4 infection and of combination sofosbuvir plus ribavirin for genotype 2 or 3 infection have been described in full-length articles.

A recent study explored the safety and efficacy of combination sofosbuvirplus ribavirin in Pakistani children (aged 5-18 years) with hepatitis C virus genotype 1, 2, or 3 infection. Further results have been presented as ab-stracts for the fixed-dose combination sofosbuvir and ledipasvir in children aged 6-11 years for the fixed-dose combination ombitasvir, pari-taprevir, and ritonavir with or without dasabuvir and with or without ribavirin in adolescents aged 12-17 years with genotype 1 or 4 infection and for combination sofosbuvir plus daclatasvir with or without ribavirin in Egyp-tian adolescents aged 12-17 years with genotype 4 infection.

Dendritic cells are professional antigen presenting cells characterized by a po-tent capacity to elicit primary T cell responses. Two major subsets of DC can be identified from human peripheral blood: plasmacytoid (p) DC and conventional or myeloid (m) DC. Each subset represents 0.3-0.5% of the normal human peripheral blood mononuclear cell (PBMC) population.

Study Timeline

• Study First Submitted: 2018-11-28
• Study First Submitted QC: 2018-12-04
• Study First Posted: 2018-12-05
• Study Start: 2018-12-06
• Primary Completion: 2019-07-02
• Study Completion: 2019-07-02
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-15
• Last Update Posted: 2019-09-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Children with chronic HCV
• age 3- 12 y old
• weight 17- 35kg
• Basal HCV viremia less than 6.8 log IU/mL
• Treatment-naive
• No cirrhosis

Exclusion Criteria

• Patients with dual HBV and HCV infection or associated with chronic hepatitis other than chronic HCV
• age below 3 years or above 12 years
• body weight less than 17 or more than 35 Kg
• HCV/HIV coinfection.
• Patients with HCV infection and HCC.
• Patients with HCV infection and underlying cardiac comorbidities
• Decompensated patients with HCV
• Hypoalbuminemia of < 3.5g/dL.
• International normalised ratio (INR) >2.
• Advanced fibrosis scoring by transient elastography (F 4 broScan)
• Any concomitant malignancy.
• Parents' refusal for participation of their children in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sofosbovir/Ledipasvir Daily	Sofosbovir/Lepipasvir (200/45mg) tablet (Heterosofir)	Patients receive oral daily dose of Sofosbovir/Ledipasvir (200/45mg) daily for 8 weeks

Primary Outcome Measures

Name	Time	Method
Side effect 3 Number of patients with nausea	8 weeks	Number of patients with nausea
Side effect 9 Number of patients with myalgia	8 weeks	Number of patients with myalgia
Side effect 10 Number of patients with dysapnea	8 weeks	Number of patients with dysapnea
Side effect 11 Number of patients with irritability	8 weeks	Number of patients with irritability
Side effect 12 Number of patients with dizziness	8 weeks	Number of patients with dizziness
Side effect 13 Number of patients with depression	8 weeks	Number of patients with depression
Side effect 1 Number of patients with fatigue	8 weeks	Number of patients with fatigue
Side effect 8 Number of patients with cough	8 weeks	Number of patients with cough
Side effect 7 Number of patients with bradycardia	8 weeks	Number of patients with bradycardia
Side effect 2 Number of patients with Headache	8 weeks	Number of patients with Headache
Side effect 4 Number of patients with diarrhea	8 weeks	Number of patients with diarrhea
Side effect 5 Number of patients with insomnia	8 weeks	Number of patients with insomnia
Side effect 6 Number of patients with weakness	8 weeks	Number of patients with weakness
Side effect 14 Number of patients with skin rash	8 weeks	Number of patients with skin rash

Secondary Outcome Measures

Name	Time	Method
HCV-RNA PCR after 20 weeks for SVR	20 weeks	HCV-RNA PCR at week 20
HCV-RNA PCR by the end of therapy	8 weeks	HCV-RNA PCR at week 8

Trial Locations

Locations (1)

Pediatric Hepatology, Gastroenterology and Nutrition Department, National Liver Institute, Menoufia University; 🇪🇬 Shebin El-Koom, Menofiya, Egypt